9-72616301-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138691.3(TMC1):c.-305-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,782 control chromosomes in the GnomAD database, including 19,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19104 hom., cov: 31)
  • Exomes 𝑓: 0.42 (3 hom.)
• Consequence: TMC1 NM_138691.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.58

Genes affected

TMC1 (HGNC:16513): (transmembrane channel like 1) This gene is considered a member of a gene family predicted to encode transmembrane proteins. The specific function of this gene is unknown; however, it is known to be required for normal function of cochlear hair cells. Mutations in this gene have been associated with progressive postlingual hearing loss and profound prelingual deafness. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 9-72616301-G-A is Benign according to our data. Variant chr9-72616301-G-A is described in ClinVar as [Benign]. Clinvar id is 1320688.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMC1	NM_138691.3	c.-305-67G>A		intron_variant		ENST00000297784.10
TMC1	XM_017014256.2	c.-91-67G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMC1	ENST00000297784.10	c.-305-67G>A		intron_variant		1	NM_138691.3	P2

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75416 AN: 151640 Hom.: 19073 Cov.: 31

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.494

GnomAD4 exome AF: 0.417 AC: 10 AN: 24 Hom.: 3 Cov.: 0 AF XY: 0.400 AC XY: 8 AN XY: 20

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.438

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.497 AC: 75494 AN: 151758 Hom.: 19104 Cov.: 31 AF XY: 0.494 AC XY: 36673 AN XY: 74166

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.495

Alfa AF: 0.465 Hom.: 27973

Bravo AF: 0.506

Asia WGS AF: 0.481 AC: 1671 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.028
Dann	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10217204; hg19: chr9-75231217;